Mitochondrial aldehyde dehydrogenase is isolated as a tetrameric enzyme but can in the presence of divalent ion cations be transformed into a more active dimericenzyme. Cytosolic enzymes are not activated. The basis for the differences in response to physiological concentrations of Mg2+ and Ca+ ions will be investigated with horse liver enzymes. Experiments to determine the in vivo state of the enzyme will be performed with rat and beef liver mitochondrial enzymes. These studies will include the use of in vivo inhibitors and in vitro hybridization of the isolated enzyme. The interrelationships between the concentration of mitochondrial aldehyde dehydrogenase and rates of aldehyde metabolism will be determined in liver slices which contain partially inactivated aldehyde dehydrogenase. An investigation of the mode of inhibition of the enzyme by various propargyl derivatives will be undertaken in order to develop potential suicide or affinity inhibitors. Lastly, the effect of alcohol on the liver isozyme pattern and molecular aggregation of aldehyde dehydrogenase will be determined in rats made dependent upon alcohol.